It is likely that many effects of polyamines in biological systems can be understood in terms of electrostatic interactions with biological polyelectrolytes, modulated by chemical and structural specificity. This approach should be particularly applicable with double-stranded DNA and RNA, which have relatively little structural variation compared to proteins or membranes, but exert profound control over cellular events. To obtain basic information on physical mechanisms by which polyamines may regulate cellular functions involving nucleic acids, we shall carry out the following studies. 1. Determine the relative importance of electrostatic and structural features (e.g., flexibility, hydrophobic methylene chains) in governing the strength of polyamine-polynucleotide interactions, by using equilibrium dialysis in Hummel-Dreyer chromatography to measure free energy, enthalpy, and entropy of binding of putrescine, spermidine, spermine, and analogs of these as functions of ionic strength. 2. Achieve a more realistic molecular interpretation of these thermodynamic parameters, by refining polyelectrolyte theories to take account of charge dispersal and internal structure of polyamines. 3. Assess the effects of polyamines on the thermal stability and intramolecular dynamics of double-stranded polynucleotides, by measuring melting transitions and hydrogen exchange kinetics. 4. Measure the dynamics of polyamine-nucleic acid interaction using NMR linewidth measurements. 5. Understand the ways in which polyamines cause and stabilize the condensation of viral and chromosomal DNA, by determining the dependence of critical collapse conditions on solvent dielectric constant, doing more realistic calculations of the balance between repulsive and attractive forces, and assessing the role of interstrand crosslinking by polyamines. 6. Assess potential roles of polyamines in regulating nucleic acid-dependent phenomena, by measuring the effects of polyamines and their derivatives on binding of drugs and proteins to DNA.